# Sacubitril/valsartan bij gevorderd HFrEF: JAMA Cardiology LIFE gerandomiseerde trial

*geplaatst 2022-01-01 · Hartfalen · JAMA cardiology · doi 10.1001/jamacardio.2021.4567 · https://hartvaat.nl/2022/01/01/sacubitril-valsartan-bij-gevorderd-hfref-jama-cardiology-life-gerandomiseerde-tr/*

JAMA Cardiology LIFE trial van sacubitril/valsartan bij patiënten met gevorderd HFrEF.

## English: Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

The LIFE trial showed that sacubitril-valsartan in patients with advanced (NYHA class IV) HFrEF is safe but does not provide significant clinical benefit beyond standard RAAS inhibition, defining the limits of ARNI therapy in end-stage heart failure.

## Abstract (original, from the publication)

IMPORTANCE: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. OBJECTIVE: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. INTERVENTION: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. MAIN OUTCOMES AND MEASURES: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. RESULTS: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. CONCLUSIONS AND RELEVANCE: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02816736.

Auteurs: Douglas L Mann, Michael M Givertz, Justin M Vader, Randall C Starling, Palak Shah, Steven E McNulty, Kevin J Anstrom, Kenneth B Margulies, Michael S Kiernan, Claudius Mahr, Divya Gupta, Margaret M Redfield, Anuradha Lala, Gregory D Lewis, Adam D DeVore, Patrice Desvigne-Nickens, Adrian F Hernandez, Eugene Braunwald

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Bron: JAMA cardiology, https://doi.org/10.1001/jamacardio.2021.4567. Bijgewerkt 2026-07-03T13:28:42Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.